In recent years, a number of lipoproteins and lipoprotein receptors have been implicated in the pathobiology of Alzheimer's disease (AD). In AD brain, we recently discovered markedly reduced expression of an ApoE receptor, LR11. In this study, we propose to use varied techniques to uncover the contribution of LR11 loss to AD pathology. Preliminary evidence suggests that LR11 expression levels regulate both amyloid precursor protein (APR), the molecule that is cleaved into beta amyloid (Ad), as well as modulating levels of Aft, a peptide widely believed to participate in the pathogenesis of AD. Our central hypothesis is that LR11 is protective against the generation of AD pathology. Specifically in Aim 1, we propose to examine the effects of LR11 on APP processing. We hypothesize that LR11 expression will protect from the amyloidogenic processing of APP. In Aim 2, we will examine if LR11 loss contributes to amyloidogenesis by assessing amyloid pathology in an LR11 deficient amyloid mouse model. We hypothesize that offspring of LR11-/-, PS1/APP mice will display a more aggressive and acclerated amyloid pathology. These studies will help elucidate the role LR11 loss plays in Alzheimer's disease pathology. [unreadable] [unreadable] [unreadable]